The proposed study represents a systematic approach to recruit subjects and develop outcome measures necessary to reach a phase I gene transfer trial in Duchenne muscular dystrophy (DMD) and in two forms of limb girdle muscular dystrophy [LGMD 2D or alpha-sarcoglycan (SG) deficiency, and LGMD 2E or beta-SG deficiency]. The prepatory stage will be carried out in years one through three of the proposal. In years four and five, Phase 1 clinical transfer trials will be done in these three forms of muscular dystrophy. The specific aims define the approach to reach the stated goals: Specific Aim 1: Identify a cohort of DMD subjects with small gene mutations to participate in Phase 1 gene transfer studies Specific Aim 2: Establish the most appropriate muscle(s) for gene transfer in a population of DMD subjects using magnetic resonance imaging (Aim 2A) and quantitative muscle strength testing (maximum voluntary isometric contraction testing or MVICT) (Aim 2B) Specific Aim 3: Identify a population of LGMD 2D (alpha-SG) and LGMD 2E (beta-SG) subjects for participation in Phase 1 gene transfer studies Specific Aim 4: Establish the most appropriate muscle(s) for gene transfer in a population of LGMD 2D and LGMD 2E subjects using magnetic resonance imaging (Aim 4A) and quantitative muscle strength testing (MVICT) (Aim 4B) Specific Aim 5: Establish appropriate delivery methods for gene transfer of adeno-associated virus (AAV) considering volume, rate, and spread of vector from the site of injection Specific Aim 6: Perform Phase 1 gene transfer trials in DMD and two forms of LGMD (2D alpha-SG) and (2E beta-SG)